CD138 promotes the accumulation and activation of autoreactive T cells in autoimmune MRL/lpr mice

Xie,Tianhong; Liu,Xin; Li,Ping

doi:10.3892/etm.2023.12267

CD138 promotes the accumulation and activation of autoreactive T cells in autoimmune MRL/lpr mice

Authors:
- Tianhong Xie
- Xin Liu
- Ping Li
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Affiliations: Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing 100010, P.R. China
Published online on: October 24, 2023 https://doi.org/10.3892/etm.2023.12267
Article Number: 568
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autoreactive T cells, specifically CD138⁺ (syndecan‑1) T cells produced in Fas‑deficient systemic lupus erythematosus (SLE) mouse models, were shown to significantly promote the generation of autoantibodies. In the present study, Murphy Roths Large lymphoproliferative (MRL/lpr) lupus mice were used to investigate the role of CD138 protein expression in T cells in the progression of SLE. Measurement of flow cytometry, immunofluorescence and Luminex were performed to determine the effect of CD138 on T cells in MRL/lpr mice. The results demonstrate that CD138⁺ T cells induce apoptosis via a Fas‑dependent pathway. CD138 protein expression in T cells of MRL/lpr mice significantly reduced T cell apoptosis and contributed to the accumulation of T cells and double negative (DN) T cells, whilst simultaneously promoting T cell activation in Fas‑deficient lupus mice. CD138 protein expression in DN T cells also significantly increased the protein expression of Fas ligand to enhance the cytotoxicity of DN T cells. Furthermore, phorbol 12‑myristate 13‑acetate and ionomycin (PI) stimulation reduced CD138 protein expression in CD3⁺ T cells and prevented CD138⁺ T cell accumulation by inducing specific apoptosis. PI stimulation also activated T cells in MRL/lpr mice to increase CD69 protein expression. CD69 protein expression in CD138⁺ T cells significantly increased the frequency of apoptotic CD138⁺ T cells. In addition, results from the present study demonstrated that CD138^‑ T cells of MRL/lpr lupus mice had an activation defect. CD138 protein expression in T cells significantly reversed the defective activation and activating T cells could significantly reduce CD138 protein expression in CD3⁺ T cells of MRL/lpr mice. This suggests that CD138 protein expression in CD3⁺CD138^‑ T cells of MRL/lpr mice may be a consequence of the impaired activation in autoreactive T cells prior to exposure to self‑antigens by the immune system. CD138 expression in autoreactive T cells has a central role in promoting the progression and development of autoimmune response in MRL/lpr mice.

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